The objectives of this proposal are 1) Improve our understanding of the pathophysiology of PVH. 2) Identify, at birth, infants at greatest risk to develop PVH. 3) Develop a method for diagnosis of PVH using biochemical and bedside monitoring. Two hypotheses are the basis for this proposal. 1) PVH-IVH in the pre-term infant is a secondary event, the initial event having occurred near the time of birth. 2) Injury to the brain cells of the pre-term infant will result in the release of brain specific creatine kinase (CK-BB) into the serum. The hypotheses will be tested by obtaining serum every twelve hours beginning at birth in pre-term infants and determining the CK-BB levels. A pilot study indicates an elevation of serum CK-BB at birth in infants who later bleed and a 2nd rise of CK-BB after the hemorrhage has occurred. In addition to following CK-BB, glutamic acid decarboxylase (GAD), another brain specific enzyme, will be followed in serum and CSF. Intracranial pressure will be monitored by means of a Ladd transducer. Computerized axial tomography (CAT) will be done to determine the presence or absence of PVH. The time of the hemorrhage in fatal cases will be determined by comparing the fraction of hemaglobin F in the clot with serial blood samples taken during life. This proposal will meet the objective by demonstrating that brain injury occurs prior to the PVH by documenting high CK-BB and GAD levels at birth in those who later develop the hemorrhage. The combination of clinical signs, CK-BB and GAD levels and intracranial pressure will allow identification of infants with hemorrhage as documented by CAT.